Pasireotide (SOM230) is a novel multi-receptor-targeted analog that has high affinity for four of the five SST receptor subtypes (SSTr1, SSTr2, SSTr3 and SSTr5); it has a 40-fold higher affinity and 158-fold higher functional activity for the SST5 receptor than octreotide. Because of its broad receptor binding profile, pasireotide may be more potent in Polycystic Liver Disease (PLD) than octreotide. In this randomized double blind placebo controlled trial the investigators will compare SOM230 treatment to placebo for 12 months in patients with PLD. The primary endpoints will be assessed at 12 months and patients receiving placebo then crossed over to SOM230, permitting all participants to receive SOM230 for the subsequent two years. Magnetic resonance imaging (MRI) will be used to assess liver volume - the primary endpoint, which will be assessed at baseline, end of years 1 and 3. This study will assess the efficacy and safety of SOM230 in reducing total liver volume and improving quality of life over 12 months. (The investigators will not be assessing efficacy at 24 months.) The therapy way be effective in PLD but also may prove to be effective for many more patients with Polycystic Kidney Disease (PKD) which will be evaluated using eGFR and kidney volume using MRI.

The investigators plan to add other sub-sites in other locations.

Eligibility

Ages Eligible for Study:

18 Years to 100 Years (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Male or female Age ≥ 18 years.

Diagnosis of PLD associated with ADPKD (meeting the Modified Ravine's criteria) or isolated ADPLD (defined by the criteria described by Reynolds et al)

Severe PLD defined as a liver volume >4000mL or symptomatic disease due to mass effects from hepatic cysts (must be able to undergo MRI or CT scan to determine this).

Not a candidate for or declining surgical intervention.

Capable of providing informed consent.

Life expectancy ≥ 12 weeks

Patients with a known history of impaired fasting blood glucose (glucose >100 and <126) may be included at the discretion of the PI. These patients should be monitored closely throughout the trial and antihyperglycemic treatment adjusted as necessary. Patients that are deemed non eligible due to elevated glucose can be re-screened after adequate medical treatment.

Adequate end organ function as defined by:

Adequate bone marrow function:

WBC ≥ 2.5 x 109/L

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

Platelets ≥ 100 x 109/L

Hb ≥ 9 g/dL

No evidence of significant liver disease:

Serum bilirubin ≤1.5 x ULN

INR < 1.3

ALT and AST ≤ 2 x ULN

Estimated glomerular filtration rate (eGFR) >30 ml/min/m2

Serum amylase and lipase ≤ 1.5 x ULN

Alkaline phosphatase ≤ 2.5 x ULN

Written informed consent obtained prior to any screening procedures

Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria:

Patients will be considered ineligible for this study if they meet any of the following criteria:

Patients with a known hypersensitivity to SST analogs or any component of the pasireotide LAR or SQ formulations.

Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.

Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.

Patients with symptomatic cholelithiasis.

Patients who are not biochemically euthyroid.

Patients with known history of hypothyroidism are eligible if they are on adequate and stable re-placement thyroid hormone therapy for at least 3 months.

Serum magnesium ≥ ULN

QT-related exclusion criteria:

QTcF at screening > 470 msec

Patients with a history of syncope or family history of idiopathic sudden death

Patients who have sustained or clinically significant cardiac arrhythmias

Patients with concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure

Family history of long QT syndrome

Concomitant medications known to prolong the QT interval.

Potassium < or = to 3.5

Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

Patients who have Uncontrolled diabetes as defined by HbA1c>8%* despite adequate therapy

Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive HIV test result (ELISA and Western blot). An HIV test will not be required; however, previous medical history will be reviewed.

Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment.

Patients who have a history of a primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. (Patients who have had no evidence of disease from primary cancer for 3 or more years are allowed to participate in the study.)

History of pancreatitis

Patients with a known history of hepatitis B or C

Presence of Hepatitis B surface antigen (HbsAg)

Presence of Hepatitis C antibody (anti-HCV)

Patients with a history of, or current, alcohol misuse/abuse within the past 12 months

Known gallbladder or bile duct disease, acute or chronic pancreatitis

Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsor's Medical Monitor

Use of an investigational drug within 1 month prior to dosing

Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670110